mRNA Display Discovery of a Novel Programmed Death Ligand 1 (PD-L1) Binding Peptide (a Peptide Ligand for PD-L1)

• DOI: 10.1021/acschembio.0c00264
• Publication Date: 2020-04-30T18:08:57Z
• Authors: Golnaz Kamalinia; Brian J. Engel; Anupallavi Sriniv...; Brian J. Grindel; Justin N. Ong; Michael A. Curran; Terry T. Takahashi; Steven W. Millward; Richard W. Roberts
• Keywords: 0301 basic medicine; Glycosylation; CHO Cells; Ligands; B7-H1 Antigen; 3. Good health; 03 medical and health sciences; Cricetulus; Animals; Humans; Biotinylation; Amino Acid Sequence; RNA, Messenger; Protein Binding

Programmed death ligand 1 (PD-L1) is a critical immune checkpoint whose overexpression on tumor cells provides mechanism of escape from surveillance. The interaction between PD-L1 and PD-1 T cell lymphocytes suppresses both activation effector function engaged by cancers to dampen antitumor immunity. Here, we used mRNA display engineer an 18-residue linear peptide that binds human PD-L1. This peptide, which term SPAM (signal peptide-based affinity maturated ligand), nonhomologous known binding peptides mAbs, with dissociation constants (KD) 119 67 nM for unglycosylated glycosylated PD-L1, respectively. highly selective shows no significant either mouse or PD-L2. Competition assays indicate the site overlaps as well therapeutic anti-PD-L1 antibodies. Taken together, these results suggest specifically could potentially serve agent PD-L1/PD-1 pathway modulator.